在本研究中，我們以電紡絲程序製備了含有亞硝基鐵氰化鈉(sodium nitroprusside, SNP)的幾丁聚醣奈米纖維，經由電紡製程的最佳化，此奈米纖維結構均勻，且能在7天內持續釋放37 µg的亞硝基鐵氰化鈉，並藉此產生具有生物功能性的一氧化氮。
為了增進奈米纖維的穩定性與機械性質，我們利用四甘醇二丙烯酸酯(tetraethylene glycol diacrylate, TTEGDA)和2,2-二甲氧基-2-苯基苯乙酮(2,2-dimethoxy-2-phenylacetophenone, DMPA)做為交聯劑與光起始劑，對混摻了亞硝基鐵氰化鈉的幾丁聚醣奈米纖維進行一步式(one-step)的紫外光交聯(photo-crosslinking)程序。根據掃描式電子顯微鏡(scanning electron microscopy, SEM)與紅外光光譜(Fourier transform infrared sprectroscopy)對奈米纖維進行膨潤分析的結果，本研究使用的光交聯程序明顯地促進了複合幾丁聚醣奈米纖維在水溶液中的穩定性，其多孔結構能在水相中維持超過24小時，而光交聯也顯祝的增進了奈米纖維的生物相容性。
相較於純幾丁聚醣奈米纖維，亞硝基鐵氰化鈉的添加促進了纖維對骨母細胞(osteoblasts, 7F2)與牙齦纖維母細胞(gingival fibroblasts, GF)的親和性。骨母細胞的活性隨著亞硝基鐵氰化鈉的添加量增加，而牙齦纖維母細胞則在亞硝基鐵氰化鈉為20%時有最佳的活性表現。螢光染色結果指出亞硝基鐵氰化鈉的添加提升了幾丁聚醣奈米纖維上的細胞貼附、延展與增生。亞硝基鐵氰化鈉亦促進了細胞鹼性磷酸酶(alkaline phosphatase, ALP)、骨橋蛋白 (osteopontin, OPN)和鈣沉積(calcium deposition)的表現，這證實了亞硝基鐵氰化鈉/幾丁聚醣奈米纖維能有效促進細胞前期、中期與後期的骨分化。

In this work, sodium nitroprusside-releasing chitosan-based (CS/SNP) nanofibers were fabricated via electrospinning. Prepared CS/SNP nanofibers were capable of sustainably releasing 37 µg SNP/mg for up to 7 days. SNP is known to release nitric oxide (NO), a radical of interest in bone tissue engineering, upon reduction and photo-degradation. NO–releasing nanofibers have been prepared previously by other groups, however their applicability to bone tissue engineering has never been investigated. This work serves to fill this gap.
To improve nanofiber stability and mechanical properties, one-step photo-crosslinking of blended CS/SNP nanofibers was carried out by addition of tetraethylene glycol diacrylate (TTEGDA) and 2,2-dimethoxy-2-phenylacetophenone (DMPA), and incorporation of UV irradiation into the electrospinning process. Photo-crosslinked nanofibers were characterized via scanning electron microscopy (SEM), Fourier transform infrared sprectroscopy and swelling test. Application of photo-crosslinking was found to significantly improve nanofiber stability in aqueous environments. SEM images revealed that the porous nanofibrous structure could be maintained up to 24 hours. Biocompatibility of CS/SNP nanofibers towards mouse osteoblasts was also significantly improved.
Addition of SNP into the nanofibrous scaffolds were found to improve their biocompatibility to osteoblasts and gingival fibroblasts (GF). Cell viability of 7F2 mouse osteoblasts and human GF cells were affected by SNP content in a dose- and time-dependent manner. MTT assays revealed that 7F2 cell viability increased with increasing SNP content, whereas GF cell viability peaked in CS/20% SNP nanofibers. Fluorescence microscope images also revealed that CS/SNP nanofibers improved cell attachment, spreading and proliferation. Osteogenic differentiation and mineralization were also enhanced by the nanofibers, as evidenced by elevated expressions of osteogenic differentiation markers including alkaline phosphatase (ALP), osteopontin (OPN) and calcium. Photo-crosslinked electrospun CS/SNP nanofibers are thus shown to have excellent potential as bone tissue engineering scaffolds.

1. Johnell, O. and J. Kanis, An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. 2006. 17: p. 17-26.
2. Surgeon-General, O.o.t., Bone Health and Osteoporosis: A Report of the Surgeon General, U.S.D.o.H.a.H. Services, Editor. 2004: Rockville, MD.
3. Shaw, C.-K., et al., Prediction of bone fracture by bone mineral density in Taiwanese. J Formos Med Assoc, 2001. 100(12): p. 805-810.
4. Porter, J.R., T.T. Ruckh, and K.C. Popat, Bone tissue engineering: A review in bone biomimetics and drug delivery strategies. Biotechnology Progress, 2009. 25(6): p. 1539-1560.
5. Lienemann, P.S., M.P. Lutolf, and M. Ehrbar, Biomimetic hydrogels for controlled biomolecule delivery to augment bone regeneration. Adv Drug Deliv Rev, 2012. 64(12): p. 1078-89.
6. Yilgor, P., et al., Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering. Biomaterials, 2009. 30(21): p. 3551-3559.
7. Srouji, S., et al., Slow-Release Human Recombinant Bone Morphogenetic Protein-2 Embedded Within Electrospun Scaffolds for Regeneration of Bone Defect: In Vitro and In Vivo Evaluation. Tissue Engineering Part A, 2010. 17(3-4): p. 269-277.
8. Kang, J., et al., Immobilization of bone morphogenetic protein on DOPA- or dopamine-treated titanium surfaces to enhance osseointegration. Biomed Res Int, 2013. 2013: p. 265980.
9. Yun, Y.-P., et al., The effect of bone morphogenic protein-2 (BMP-2)-immobilizing heparinized-chitosan scaffolds for enhanced osteoblast activity. Tissue Engineering and Regenerative Medicine, 2013. 10(3): p. 122-130.
10. Fan, J., et al., Adipose-Derived Stem Cells and BMP-2 Delivery in Chitosan-Based 3D Constructs to Enhance Bone Regeneration in a Rat Mandibular Defect Model. Tissue Engineering Part A, 2014. 20(15-16): p. 2169-2179.
11. Tejeda-Montes, E., et al., Bioactive membranes for bone regeneration applications: Effect of physical and biomolecular signals on mesenchymal stem cell behavior. Acta Biomaterialia, 2014. 10(1): p. 134-141.
12. Li, C.H., et al., Immobilization of naringin onto chitosan substrates by using ozone activation. Colloids Surf B Biointerfaces, 2014. 115: p. 1-7.
13. Li, L., et al., Controlled dual delivery of BMP-2 and dexamethasone by nanoparticle-embedded electrospun nanofibers for the efficient repair of critical-sized rat calvarial defect. Biomaterials, 2015. 37(0): p. 218-229.
14. Evans, D.M. and S.H. Ralston, Nitric Oxide and Bone. Journal of Bone and Mineral Research, 1996. 11: p. 300-305.
15. Saura, M., C. Tarin, and C. Zaragoza, Recent insights into the implication of nitric oxide in osteoblast differentiation and proliferation during bone development. ScientificWorldJournal, 2010. 10: p. 624-32.
16. Wimalawansa, S.J., Nitric oxide: novel therapy for osteoporosis. Expert Opin Pharmacother, 2008. 9(17): p. 3025-44.
17. Diwan, A.D., et al., Nitric Oxide Modulates Fracture Healing. Journal of Bone and Mineral Research, 2000. 15: p. 342-351.
18. Park, J.-W. and G. Means, Reaction of drugs with sodium nitroprusside as a source of nitrosamines. Archives of Pharmacal Research, 1991. 14(2): p. 118-123.
19. Leeuwenkamp, O.R., et al., Nitroprusside, antihypertensive drug and analytical reagent. Review of (photo)stability, pharmacology and analytical properties. Pharm Weekbl Sci, 1984. 6(4): p. 129-40.
20. TAYLOR, T.H., M. STYLES, and A.J. LAMMING, SODIUM NITROPRUSSIDE AS A HYPOTENSIVE AGENT IN GENERAL ANAESTHESIA. British Journal of Anaesthesia, 1970. 42(10): p. 859-864.
21. Rőszer, T., Nitric Oxide Signaling and Nitrosative Stress in the Musculoskeletal System, in Systems Biology of Free Radicals and Antioxidants, I. Laher, Editor. 2014, Springer Berlin Heidelberg. p. 2895-2926.
22. Felka, T., et al., Nitric Oxide Activates Signaling by c-Raf, MEK, p-JNK, p38 MAPK and p53 in Human Mesenchymal Stromal Cells inhibits their Osteogenic Differentiation by Blocking Expression of Runx2. Journal of Stem Cell Research & Therapy, 2014. 04(04).
23. Aitken, D., et al., Cyanide toxicity following nitroprusside induced hypotension. Can Anaesth Soc J, 1977. 24(6): p. 651-60.
24. Lu, Y., D.L. Slomberg, and M.H. Schoenfisch, Nitric oxide-releasing chitosan oligosaccharides as antibacterial agents. Biomaterials, 2014. 35(5): p. 1716-1724.
25. Lu, Y., et al., Nitric Oxide-Releasing Amphiphilic Poly(amidoamine) (PAMAM) Dendrimers as Antibacterial Agents. Biomacromolecules, 2013. 14(10): p. 3589-3598.
26. Nablo, B.J., et al., Inhibition of implant-associated infections via nitric oxide release. Biomaterials, 2005. 26(34): p. 6984-6990.
27. Worley, B.V., D.L. Slomberg, and M.H. Schoenfisch, Nitric Oxide-Releasing Quaternary Ammonium-Modified Poly(amidoamine) Dendrimers as Dual Action Antibacterial Agents. Bioconjugate Chemistry, 2014. 25(5): p. 918-927.
28. Thierry, B., et al., Biodegradable membrane-covered stent from chitosan-based polymers. Journal of Biomedical Materials Research Part A, 2005. 75A(3): p. 556-566.
29. Lowe, A., et al., Coated melt-spun acrylonitrile-based suture for delayed release of nitric oxide. Materials Letters, 2014. 125(0): p. 221-223.
30. Koh, A., et al., Nitric Oxide-Releasing Silica Nanoparticle-Doped Polyurethane Electrospun Fibers. ACS Applied Materials & Interfaces, 2013. 5(16): p. 7956-7964.
31. Koh, A., Y. Lu, and M.H. Schoenfisch, Fabrication of Nitric Oxide-Releasing Porous Polyurethane Membranes-Coated Needle-type Implantable Glucose Biosensors. Analytical Chemistry, 2013. 85(21): p. 10488-10494.
32. Liu, H.A. and K.J. Balkus, Novel Delivery System for the Bioregulatory Agent Nitric Oxide. Chemistry of Materials, 2009. 21(21): p. 5032-5041.
33. Baldik, Y., et al., Deletion of iNOS gene impairs mouse fracture healing. Bone, 2005. 37(1): p. 32-36.
34. Akins, R. and J. Rabolt, Chapter I.2.16 - Electrospinning Fundamentals and Applications A2 - Lemons, Buddy D. RatnerAllan S. HoffmanFrederick J. SchoenJack E, in Biomaterials Science (Third Edition). 2013, Academic Press. p. 332-339.
35. Chung, T.-W., et al., Growth of Human Endothelial Cells on Different Concentrations of Gly-Arg-Gly-Asp Grafted Chitosan Surface. Artificial Organs, 2003. 27(2): p. 155-161.
36. Lehr, C.-M., et al., In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. International Journal of Pharmaceutics, 1992. 78(1): p. 43-48.
37. He, P., S.S. Davis, and L. Illum, In vitro evaluation of the mucoadhesive properties of chitosan microspheres. International Journal of Pharmaceutics, 1998. 166(1): p. 75-88.
38. Ho, M.H., et al., Improving effects of chitosan nanofiber scaffolds on osteoblast proliferation and maturation. Int J Nanomedicine, 2014. 9: p. 4293-304.
39. Ignarro, L.J., Nitric Oxide: A Unique Endogenous Signaling Molecule in Vascular Biology (Nobel Lecture). Angewandte Chemie International Edition, 1999. 38(13-14): p. 1882-1892.
40. Walford, G. and J. Loscalzo, Nitric oxide in vascular biology. Journal of Thrombosis and Haemostasis, 2003. 1(10): p. 2112-2118.
41. Fang, F.C., Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity. The Journal of Clinical Investigation, 1997. 99(12): p. 2818-2825.
42. Luo, J.-d. and A.F. Chen, Nitric oxide: a newly discovered function on wound healing. Acta Pharmacol Sin, 2005. 26(3): p. 259-264.
43. Mocellin, S., V. Bronte, and D. Nitti, Nitric oxide, a double edged sword in cancer biology: Searching for therapeutic opportunities. Medicinal Research Reviews, 2007. 27(3): p. 317-352.
44. Fleming, I., Molecular mechanisms underlying the activation of eNOS. Pflügers Archiv - European Journal of Physiology, 2009. 459(6): p. 793-806.
45. Alderton, W.K., C.E. Cooper, and R.G. Knowles, Nitric oxide synthases: structure, function and inhibition. Biochemical Journal, 2001. 357(3): p. 593-615.
46. MacPherson, H., B.S. Noble, and S.H. Ralston, Expression and Functional Role of Nitric Oxide Synthase Isoforms in Human Osteoblast-like Cells. Bone, 1999. 24(3): p. 179-185.
47. Nathan, C. and Q.W. Xie, Regulation of biosynthesis of nitric oxide. Journal of Biological Chemistry, 1994. 269(19): p. 13725-13728.
48. Damoulis, P.D. and P.V. Hauschka, Nitric Oxide Acts in Conjunction with Proinflammatory Cytokines to Promote Cell Death in Osteoblasts. Journal of Bone and Mineral Research, 1997. 12(3): p. 412-422.
49. Chae, H.-J., et al., Nitric Oxide is a Regulator of Bone Remodelling. Journal of Pharmacy and Pharmacology, 1997. 49(9): p. 897-902.
50. Denninger, J.W. and M.A. Marletta, Guanylate cyclase and the ⋅NO/cGMP signaling pathway. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1999. 1411(2–3): p. 334-350.
51. Ke, X., et al., Nitric oxide regulates actin reorganization through cGMP and Ca2+/calmodulin in RAW 264.7 cells. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2001. 1539(1–2): p. 101-113.
52. Gertsberg, I., et al., Intracellular Ca2+ Regulates the Phosphorylation and the Dephosphorylation of Ciliary Proteins Via the NO Pathway. The Journal of General Physiology, 2004. 124(5): p. 527-540.
53. Ding, H., et al., NO-beta-catenin crosstalk modulates primitive streak formation prior to embryonic stem cell osteogenic differentiation. J Cell Sci, 2012. 125(Pt 22): p. 5564-77.
54. Zou, L., et al., Molecular Mechanism of Osteochondroprogenitor Fate Determination During Bone Formation, in Tissue Engineering, J.P. Fisher, Editor. 2007, Springer US: Boston, MA. p. 431-441.
55. Afzal, F., J. Polak, and L. Buttery, Endothelial nitric oxide synthase in the control of osteoblastic mineralizing activity and bone integrity. The Journal of Pathology, 2004. 202(4): p. 503-510.
56. Aguirre, J., et al., Endothelial Nitric Oxide Synthase Gene-Deficient Mice Demonstrate Marked Retardation in Postnatal Bone Formation, Reduced Bone Volume, and Defects in Osteoblast Maturation and Activity. The American Journal of Pathology, 2001. 158(1): p. 247-257.
57. Riancho, J.A., et al., Expression and functional role of nitric oxide synthase in osteoblast-like cells. Journal of Bone and Mineral Research, 1995. 10(3): p. 439-446.
58. Hikiji, H., et al., Direct action of nitric oxide on osteoblastic differentiation. FEBS Letters, 1997. 410(2-3): p. 238-242.
59. Otsuka, E., et al., Effects of nitric oxide from exogenous nitric oxide donors on osteoblastic metabolism. European Journal of Pharmacology, 1998. 349(2–3): p. 345-350.
60. Otsuka, E., et al., Characterization of osteoblastic differentiation of stromal cell line ST2 that is induced by ascorbic acid. American Journal of Physiology - Cell Physiology, 1999. 277(1): p. C132-C138.
61. Joiner, D.M., et al., Bone marrow stromal cells from aged male rats have delayed mineralization and reduced response to mechanical stimulation through nitric oxide and ERK1/2 signaling during osteogenic differentiation. Biogerontology, 2012. 13(5): p. 467-478.
62. Teixeira, C.C., H. Agoston, and F. Beier, Nitric oxide, C-type natriuretic peptide and cGMP as regulators of endochondral ossification. Developmental Biology, 2008. 319(2): p. 171-178.
63. Wang, G., et al., Inducible nitric oxide synthase–nitric oxide signaling mediates the mitogenic activity of Rac1 during endochondral bone growth. Journal of Cell Science, 2011. 124(20): p. 3405-3413.
64. Yan, Q., Q. Feng, and F. Beier, Endothelial nitric oxide synthase deficiency in mice results in reduced chondrocyte proliferation and endochondral bone growth. Arthritis & Rheumatism, 2010. 62(7): p. 2013-2022.
65. Yan, Q., Q. Feng, and F. Beier, Reduced chondrocyte proliferation, earlier cell cycle exit and increased apoptosis in neuronal nitric oxide synthase-deficient mice. Osteoarthritis and Cartilage, 2012. 20(2): p. 144-151.
66. Chen, R.-M., et al., Molecular mechanism of nitric oxide-induced osteoblast apoptosis. Journal of Orthopaedic Research, 2005. 23(2): p. 462-468.
67. Chen, R.M., et al., Nitric oxide induces osteoblast apoptosis through the de novo synthesis of Bax protein. Journal of Orthopaedic Research, 2002. 20(2): p. 295-302.
68. Cherng, Y.G., et al., Apoptotic insults to human chondrocytes induced by sodium nitroprusside are involved in sequential events, including cytoskeletal remodeling, phosphorylation of mitogen-activated protein kinase kinase kinase-1/c-Jun N-terminal kinase, and Bax-mitochondria-mediated caspase activation. Journal of Orthopaedic Research, 2008. 26(7): p. 1018-1026.
69. Sullivan, K., et al., JNK inhibitors increase osteogenesis in Nf1-deficient cells. Bone, 2011. 49(6): p. 1311-1316.
70. Wang, P.G., et al., Nitric Oxide Donors:  Chemical Activities and Biological Applications. Chemical Reviews, 2002. 102(4): p. 1091-1134.
71. Wold, K.A., et al., Fabrication of Biodegradable Polymeric Nanofibers with Covalently Attached NO Donors. ACS Applied Materials & Interfaces, 2012. 4(6): p. 3022-3030.
72. Bahnson, E.S.M., et al., Targeted Nitric Oxide Delivery by Supramolecular Nanofibers for the Prevention of Restenosis After Arterial Injury. Antioxidants & Redox Signaling, 2015. 24(8): p. 401-418.
73. Broniowska, K.A., A.R. Diers, and N. Hogg, S-nitrosoglutathione. Biochim Biophys Acta, 2013. 1830(5): p. 3173-81.
74. Bartberger, M.D., et al., S-N dissociation energies of S-nitrosothiols: on the origins of nitrosothiol decomposition rates. J Am Chem Soc, 2001. 123(36): p. 8868-9.
75. Stamler, J., D. Singel, and J. Loscalzo, Biochemistry of nitric oxide and its redox-activated forms. Science, 1992. 258(5090): p. 1898-1902.
76. Seabra, A.B., et al., S-nitrosoglutathione incorporated in poly(ethylene glycol) matrix: potential use for topical nitric oxide delivery. Nitric Oxide, 2004. 11(3): p. 263-72.
77. Loan, T.T.K., et al., Micro-ring disc ultramicroelectrodes array for direct detection of NO-release from S-nitrosoglutathione. Electrochemistry Communications, 2011. 13(7): p. 681-684.
78. Zhelyaskov, V.R. and D.W. Godwin, A Nitric Oxide Concentration Clamp. Nitric Oxide, 1999. 3(5): p. 419-425.
79. Feelisch, M., The Biochemical Pathways of Nitric Oxide Formation from Nitrovasodilators: Appropriate Choice of Exogenous NO Donors and Aspects of Preparation and Handling of Aqueous NO Solutions. Journal of Cardiovascular Pharmacology, 1991. 17: p. S25&hyhen;S33.
80. Vesey, C.J. and G.A. Batistoni, The determination and stability of sodium nitroprusside in aqueous solutions (Determination and Stability of SNP). Journal of Clinical Pharmacy and Therapeutics, 1977. 2(2): p. 105-117.
81. Bates, J.N., et al., Nitric oxide generation from nitroprusside by vascular tissue. Evidence that reduction of the nitroprusside anion and cyanide loss are required. Biochem Pharmacol, 1991. 42 Suppl: p. S157-65.
82. Johnson, M.D. and R.G. Wilkins, Kinetics of the primary interaction of pentacyanonitrosylferrate(2-) (nitroprusside) with aliphatic thiols. Inorganic Chemistry, 1984. 23(2): p. 231-235.
83. Szacilowski, K., et al., Photochemistry of the [Fe(CN)(5)NO](2-)-thiolate system. Journal of the Chemical Society-Dalton Transactions, 1999(14): p. 2353-2357.
84. Rochelle, L.G., et al., Bioactivation of Nitroprusside by Porcine Endothelial-Cells. Toxicology and Applied Pharmacology, 1994. 128(1): p. 123-128.
85. Kleshchev, A.L., et al., Reduction of sodium nitroprusside with the subsequent elimination of nitric oxide in animals. Zhurnal Fizicheskoi Khimii, 1985. 59(2): p. 462-467.
86. Rao, D.N.R., S. Elguindi, and P.J. O'Brien, Reductive metabolism of nitroprusside in rat hepatocytes and human erythrocytes. Archives of Biochemistry and Biophysics, 1991. 286(1): p. 30-37.
87. Kowaluk, E.A., P. Seth, and H.L. Fung, Metabolic activation of sodium nitroprusside to nitric oxide in vascular smooth muscle. Journal of Pharmacology and Experimental Therapeutics, 1992. 262(3): p. 916-922.
88. Mohazzab-H., K.M., et al., Potential Role of a Membrane-Bound NADH Oxidoreductase in Nitric Oxide Release and Arterial Relaxation to Nitroprusside. Circulation Research, 1999. 84(2): p. 220-228.
89. Babich, H., et al., In vitro toxicity of sodium nitroprusside to human endothelial ECV304 cells. Environmental Toxicology and Pharmacology, 1998. 5(2): p. 135-144.
90. Mitra, R.P., et al., Photolysis of sodium nitroprusside and nitroprussic acid. Journal of Inorganic and Nuclear Chemistry, 1963. 25(10): p. 1263-1266.
91. Frank, M.J., J.B. Johnson, and S.H. Rubin, Spectrophotometric determination of sodium nitroprusside and its photodegradation products. Journal of Pharmaceutical Sciences, 1976. 65(1): p. 44-48.
92. Slomberg, D.L., et al., Role of Size and Shape on Biofilm Eradication for Nitric Oxide-Releasing Silica Nanoparticles. ACS Applied Materials & Interfaces, 2013. 5(19): p. 9322-9329.
93. Worley, B.V., K.M. Schilly, and M.H. Schoenfisch, Anti-Biofilm Efficacy of Dual-Action Nitric Oxide-Releasing Alkyl Chain Modified Poly(amidoamine) Dendrimers. Molecular Pharmaceutics, 2015. 12(5): p. 1573-1583.
94. Tan, L., et al., Novel quantum dots–carboxymethyl chitosan nanocomposite nitric oxide donors capable of detecting release of nitric oxide in situ. Acta Biomaterialia, 2012. 8(10): p. 3744-3753.
95. Tan, L., A. Wan, and H. Li, Fluorescent chitosan complex nanosphere diazeniumdiolates as donors and sensitive real-time probes of nitric oxide. Analyst, 2013. 138(3): p. 879-886.
96. Cojocariu, A., et al., Evaluation of crosslinked chitosan hydrogels as carriers for prolonged delivery of some novel nitric oxide donor compounds based on theophylline and paracetamol. e-Polymers, 2011. 11(1): p. 334-351.
97. Thierry, B., et al., Bioactive Coatings of Endovascular Stents Based on Polyelectrolyte Multilayers. Biomacromolecules, 2003. 4: p. 1564-1571.
98. Fix, S.M., M.A. Borden, and P.A. Dayton, Therapeutic gas delivery via microbubbles and liposomes. Journal of Controlled Release, 2015. 209(0): p. 139-149.
99. Li, L. and C.-C. Chu, Nitroxyl Radical Incorporated Electrospun Biodegradable Poly(ester Amide) Nanofiber Membranes. Journal of Biomaterials Science, Polymer Edition, 2009. 20(3): p. 341-361.
100. Kushwaha, M., et al., A nitric oxide releasing, self assembled peptide amphiphile matrix that mimics native endothelium for coating implantable cardiovascular devices. Biomaterials, 2010. 31(7): p. 1502-1508.
101. López-Jaramillo, P., et al., A Controlled, Randomized-Blinded Clinical Trial to Assess the Efficacy of a Nitric Oxide Releasing Patch in the Treatment of Cutaneous Leishmaniasis by Leishmania (V.) panamensis. The American Journal of Tropical Medicine and Hygiene, 2010. 83(1): p. 97-101.
102. Andukuri, A., et al., A hybrid biomimetic nanomatrix composed of electrospun polycaprolactone and bioactive peptide amphiphiles for cardiovascular implants. Acta Biomaterialia, 2011. 7(1): p. 225-233.
103. Coneski, P.N., J.A. Nash, and M.H. Schoenfisch, Nitric Oxide-Releasing Electrospun Polymer Microfibers. ACS Applied Materials & Interfaces, 2011. 3(2): p. 426-432.
104. Vogt, C., et al., Fabrication and Characterization of a Nitric Oxide-Releasing Nanofibrous Gelatin Matrix. Biomacromolecules, 2013. 14(8): p. 2521-2530.
105. Dolanský, J., et al., Polystyrene Nanofiber Materials for Visible-Light-Driven Dual Antibacterial Action via Simultaneous Photogeneration of NO and O2(1Δg). ACS Applied Materials & Interfaces, 2015. 7(41): p. 22980-22989.
106. Worley, B.V., et al., Active Release of Nitric Oxide-Releasing Dendrimers from Electrospun Polyurethane Fibers. ACS Biomaterials Science & Engineering, 2016. 2(3): p. 426-437.
107. Ramakrishna, S., et al., An introduction to electrospinning and nanofibers. Vol. 90. 2005: World Scientific.
108. Greiner, A. and J.H. Wendorff, Electrospinning: A Fascinating Method for the Preparation of Ultrathin Fibers. Angewandte Chemie International Edition, 2007. 46(30): p. 5670-5703.
109. Schreuder-Gibson, H., et al., Protective textile materials based on electrospun nanofibers. Journal of Advanced Materials, 2002. 34(3): p. 44-55.
110. Ma, Z., M. Kotaki, and S. Ramakrishna, Electrospun cellulose nanofiber as affinity membrane. Journal of Membrane Science, 2005. 265(1–2): p. 115-123.
111. Gopal, R., et al., Electrospun nanofibrous filtration membrane. Journal of Membrane Science, 2006. 281(1–2): p. 581-586.
112. Gopal, R., et al., Electrospun nanofibrous polysulfone membranes as pre-filters: Particulate removal. Journal of Membrane Science, 2007. 289(1–2): p. 210-219.
113. Aussawasathien, D., C. Teerawattananon, and A. Vongachariya, Separation of micron to sub-micron particles from water: Electrospun nylon-6 nanofibrous membranes as pre-filters. Journal of Membrane Science, 2008. 315(1–2): p. 11-19.
114. Pham-Huu, C., et al., Carbon nanofiber supported palladium catalyst for liquid-phase reactions. An active and selective catalyst for hydrogenation of C = C bonds. Chemical Communications, 2000(19): p. 1871-1872.
115. Ostermann, R., et al., V2O5 nanorods on TiO2 nanofibers: A new class of hierarchical nanostructures enabled by electrospinning and calcination. Nano Letters, 2006. 6(6): p. 1297-1302.
116. Oh, G.Y., et al., Preparation of the novel manganese-embedded PAN-based activated carbon nanofibers by electrospinning and their toluene adsorption. Journal of Analytical and Applied Pyrolysis, 2008. 81(2): p. 211-217.
117. Liu, H.Q., et al., ZnO nanofiber and nanoparticle synthesized through electrospinning and their photocatalytic activity under visible light. Journal of the American Ceramic Society, 2008. 91(4): p. 1287-1291.
118. Guler, M.O. and S.I. Stupp, A Self-Assembled Nanofiber Catalyst for Ester Hydrolysis. Journal of the American Chemical Society, 2007. 129(40): p. 12082-12083.
119. Tajima, T. and N. Kusamoto, Fiber, fiber assembly, and fiber producing method. 2009: US.
120. Lee, S. and S.K. Obendorf, Developing protective textile materials as barriers to liquid penetration using melt-electrospinning. Journal of Applied Polymer Science, 2006. 102(4): p. 3430-3437.
121. Gorji, M., A.A.A. Jeddi, and A.A. Gharehaghaji, Fabrication and characterization of polyurethane electrospun nanofiber membranes for protective clothing applications. Journal of Applied Polymer Science, 2012. 125(5): p. 4135-4141.
122. Kim, Y.W., M.S. Gong, and B.K. Choi, Ionic conduction and electrochemical properties of new poly(acrylonitrile-itaconate)-based gel polymer electrolytes. Journal of Power Sources, 2001. 97–98: p. 654-656.
123. Choi, S.-S., et al., Silica nanofibers from electrospinning/sol-gel process. Journal of Materials Science Letters, 2003. 22(12): p. 891-893.
124. Choi, S.W., et al., An Electrospun Poly(vinylidene fluoride) Nanofibrous Membrane and Its Battery Applications. Advanced Materials, 2003. 15(23): p. 2027-2032.
125. Choi, S.-S., et al., Electrospun PVDF nanofiber web as polymer electrolyte or separator. Electrochimica Acta, 2004. 50(2–3): p. 339-343.
126. Hong, K.H., K.W. Oh, and T.J. Kang, Preparation of conducting nylon-6 electrospun fiber webs by the in situ polymerization of polyaniline. Journal of Applied Polymer Science, 2005. 96(4): p. 983-991.
127. Raghavan, P., et al., Ionic conductivity and electrochemical properties of nanocomposite polymer electrolytes based on electrospun poly(vinylidene fluoride-co-hexafluoropropylene) with nano-sized ceramic fillers. Electrochimica Acta, 2008. 54(2): p. 228-234.
128. Sun Jong, K., et al. A novel polymer nanofiber interface for chemical sensor applications. in Frequency Control Symposium and Exhibition, 2000. Proceedings of the 2000 IEEE/EIA International. 2000.
129. Lee, S.-H., et al., Design, Synthesis and Electrospinning of a Novel Fluorescent Polymer for Optical Sensor Applications. MRS Online Proceedings Library Archive, 2001. 708: p. null-null.
130. Wang, X., et al., Electrospun Nanofibrous Membranes for Highly Sensitive Optical Sensors. Nano Letters, 2002. 2(11): p. 1273-1275.
131. Gouma, P.I., Nanostructured polymorphic oxides for advanced chemosensors. Reviews on Advanced Materials Science, 2003. 5(2): p. 147-154.
132. Ding, B., et al., Electrospun nanofibrous membranes coated quartz crystal microbalance as gas sensor for NH3 detection. Sensors and Actuators B: Chemical, 2004. 101(3): p. 373-380.
133. Ding, B., M. Yamazaki, and S. Shiratori, Electrospun fibrous polyacrylic acid membrane-based gas sensors. Sensors and Actuators B: Chemical, 2005. 106(1): p. 477-483.
134. Kowalczyk, T., et al., Electrospinning of bovine serum albumin optimization and the use for production of biosensors. Biomacromolecules, 2008. 9(7): p. 2087-2090.
135. Rojas, R. and N.J. Pinto, Using Electrospinning for the Fabrication of Rapid Response Gas Sensors Based on Conducting Polymer Nanowires. Sensors Journal, IEEE, 2008. 8(6): p. 951-953.
136. Wang, X., et al., A highly sensitive humidity sensor based on a nanofibrous membrane coated quartz crystal microbalance. Nanotechnology, 2010. 21(5): p. 055502.
137. Chung, J.-H., H.-B. Lee, and J.-H. Kim, Electrohydrodynamic Assembly of Nanoparticles for Nanoengineered Biosensors, in Multiscale Simulations and Mechanics of Biological Materials. 2013, John Wiley & Sons Ltd. p. 193-206.
138. Liang, D., B.S. Hsiao, and B. Chu, Functional electrospun nanofibrous scaffolds for biomedical applications. Advanced Drug Delivery Reviews, 2007. 59(14): p. 1392-1412.
139. Ma, Z., et al., Potential of nanofiber matrix as tissue-engineering scaffolds. Tissue Eng, 2005. 11(1-2): p. 101-9.
140. Zhang, Y., et al., Recent development of polymer nanofibers for biomedical and biotechnological applications. Journal of Materials Science: Materials in Medicine, 2005. 16(10): p. 933-946.
141. Venugopal, J.R., et al., Nanobioengineered Electrospun Composite Nanofibers and Osteoblasts for Bone Regeneration. Artificial Organs, 2008. 32(5): p. 388-397.
142. Ghasemi-Mobarakeh, L., et al., Advances in electrospun nanofibers for bone and cartilage regeneration. J Nanosci Nanotechnol, 2013. 13(7): p. 4656-71.
143. Zamani, M., M.P. Prabhakaran, and S. Ramakrishna, Advances in drug delivery via electrospun and electrosprayed nanomaterials. Int J Nanomedicine, 2013. 8: p. 2997-3017.
144. Sridhar, R., et al., Electrosprayed nanoparticles and electrospun nanofibers based on natural materials: applications in tissue regeneration, drug delivery and pharmaceuticals. Chemical Society Reviews, 2015.
145. Holmes, B., et al., Electrospun fibrous scaffolds for bone and cartilage tissue generation: recent progress and future developments. Tissue Eng Part B Rev, 2012. 18(6): p. 478-86.
146. Hu, X., et al., Electrospinning of polymeric nanofibers for drug delivery applications. Journal of Controlled Release, 2014. 185(0): p. 12-21.
147. Nayak, R., et al., Recent advances in nanofibre fabrication techniques. Textile Research Journal, 2012. 82(2): p. 129-147.
148. Formhals, A., Process and apparatus for preparing artificial threads. 1934, Google Patents: US.
149. Sun, Z., et al., Compound Core–Shell Polymer Nanofibers by Co-Electrospinning. Advanced Materials, 2003. 15(22): p. 1929-1932.
150. Bognitzki, M., et al., Nanostructured fibers via electrospinning. Advanced Materials, 2001. 13(1): p. 70-+.
151. Boland, E.D., et al., Tailoring tissue engineering scaffolds using electrostatic processing techniques: A study of poly(glycolic acid) electrospinning. Journal of Macromolecular Science-Pure and Applied Chemistry, 2001. 38(12): p. 1231-1243.
152. Hohman, M.M., et al., Electrospinning and electrically forced jets. I. Stability theory. Physics of Fluids (1994-present), 2001. 13(8): p. 2201-2220.
153. Hohman, M.M., et al., Electrospinning and electrically forced jets. II. Applications. Physics of Fluids (1994-present), 2001. 13(8): p. 2221-2236.
154. J., D. and R. DH., Electospinning process and application of electrospun fibers. J Electrostat, 1995. 35: p. 151-160.
155. Yarin, A.L., S. Koombhongse, and D.H. Reneker, Taylor cone and jetting from liquid droplets in electrospinning of nanofibers. Journal of Applied Physics, 2001. 90(9): p. 4836-4846.
156. Reneker, D.H., et al., Bending instability of electrically charged liquid jets of polymer solutions in electrospinning. Journal of Applied Physics, 2000. 87(9): p. 4531-4547.
157. Yarin, A.L., S. Koombhongse, and D.H. Reneker, Bending instability in electrospinning of nanofibers. Journal of Applied Physics, 2001. 89(5): p. 3018-3026.
158. Zeleny, J., The Electrical Discharge from Liquid Points, and a Hydrostatic Method of Measuring the Electric Intensity at Their Surfaces. Physical Review, 1914. 3(2): p. 69-91.
159. Shin, Y.M., et al., Electrospinning: A whipping fluid jet generates submicron polymer fibers. Applied Physics Letters, 2001. 78(8): p. 1149-1151.
160. Frenot, A. and I.S. Chronakis, Polymer nanofibers assembled by electrospinning. Current Opinion in Colloid & Interface Science, 2003. 8(1): p. 64-75.
161. Ramakrishna, S., et al., Electrospun nanofibers: solving global issues. Materials Today, 2006. 9(3): p. 40-50.
162. J., K. and C. HG., Fabrication of oriented polymeric nanofibers on planer surfaces by electrospinning. Appl Phys Lett., 2003. 83: p. 371-373.
163. Fridrikh, S.V., et al., Controlling the Fiber Diameter during Electrospinning. Physical Review Letters, 2003. 90(14): p. 144502.
164. Katti, D.S., et al., Bioresorbable nanofiber-based systems for wound healing and drug delivery: Optimization of fabrication parameters. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2004. 70B(2): p. 286-296.
165. Zong, X., et al., Structure and process relationship of electrospun bioabsorbable nanofiber membranes. Polymer, 2002. 43(16): p. 4403-4412.
166. Larrondo, L. and R. St. John Manley, Electrostatic fiber spinning from polymer melts. I. Experimental observations on fiber formation and properties. Journal of Polymer Science: Polymer Physics Edition, 1981. 19(6): p. 909-920.
167. Mit-uppatham, C., M. Nithitanakul, and P. Supaphol, Ultrafine Electrospun Polyamide-6 Fibers: Effect of Solution Conditions on Morphology and Average Fiber Diameter. Macromolecular Chemistry and Physics, 2004. 205(17): p. 2327-2338.
168. Baumgarten, P.K., Electrostatic spinning of acrylic microfibers. Journal of Colloid and Interface Science, 1971. 36(1): p. 71-79.
169. Deitzel, J.M., et al., The effect of processing variables on the morphology of electrospun nanofibers and textiles. Polymer, 2001. 42(1): p. 261-272.
170. Demir, M.M., et al., Electrospinning of polyurethane fibers. Polymer, 2002. 43(11): p. 3303-3309.
171. Zhao, S.L., et al., Electrospinning of ethyl-cyanoethyl cellulose/tetrahydrofuran solutions. Journal of Applied Polymer Science, 2004. 91(1): p. 242-246.
172. Sukigara, S., et al., Regeneration of Bombyx mori silk by electrospinning—part 1: processing parameters and geometric properties. Polymer, 2003. 44(19): p. 5721-5727.
173. Jarusuwannapoom, T., et al., Effect of solvents on electro-spinnability of polystyrene solutions and morphological appearance of resulting electrospun polystyrene fibers. European Polymer Journal, 2005. 41(3): p. 409-421.
174. Huang, L., et al., Engineered collagen-PEO nanofibers and fabrics. Journal of Biomaterials Science-Polymer Edition, 2001. 12(9): p. 979-993.
175. Buchko, C.J., et al., Processing and microstructural characterization of porous biocompatible protein polymer thin films. Polymer, 1999. 40(26): p. 7397-7407.
176. Krishnappa, R.V.N., K. Desai, and C.M. Sung, Morphological study of electrospun polycarbonates as a function of the solvent and processing voltage. Journal of Materials Science, 2003. 38(11): p. 2357-2365.
177. Yuan, X., et al., Morphology of ultrafine polysulfone fibers prepared by electrospinning. Polymer International, 2004. 53(11): p. 1704-1710.
178. Ki, C.S., et al., Characterization of gelatin nanofiber prepared from gelatin–formic acid solution. Polymer, 2005. 46(14): p. 5094-5102.
179. Lee, J.S., et al., Role of molecular weight of atactic poly(vinyl alcohol) (PVA) in the structure and properties of PVA nanofabric prepared by electrospinning. Journal of Applied Polymer Science, 2004. 93(4): p. 1638-1646.
180. Kurita, K., T. Sannan, and Y. Iwakura, Studies on chitin, 4. Evidence for formation of block and random copolymers of N-acetyl-D-glucosamine and D-glucosamine by hetero- and homogeneous hydrolyses. Die Makromolekulare Chemie, 1977. 178(12): p. 3197-3202.
181. Vårum, K.M., et al., 13C-N.m.r. studies of the acetylation sequences in partially N-deacetylated chitins (chitosans). Carbohydrate Research, 1991. 217(0): p. 19-27.
182. Araki, Y. and E. Ito, A pathway of chitosan formation in Mucor rouxii: Enzymatic deacetylation of chitin. Biochemical and Biophysical Research Communications, 1974. 56(3): p. 669-675.
183. Li, D. and Y. Xia, Electrospinning of Nanofibers: Reinventing the Wheel? Advanced Materials, 2004. 16(14): p. 1151-1170.
184. S. , K.F., W. E. Teo, C. T. Lim and Z. Ma, An introduction to electrospinning and nanofibers. World Scientific, 2005.
185. Kim, S.H., et al., Correlation of proliferation, morphology and biological responses of fibroblasts on LDPE with different surface wettability. Journal of Biomaterials Science, Polymer Edition, 2007. 18(5): p. 609-622.
186. Guibal, E., Interactions of metal ions with chitosan-based sorbents: a review. Separation and Purification Technology, 2004. 38(1): p. 43-74.
187. Li, D. and Y. Xia, Electrospinning of Nanofibers: Reinventing the Wheel? Advanced Materials. Vol. 16. 2004: WILEY-VCH Verlag. 1151-1170.
188. Qun, G. and W. Ajun, Effects of molecular weight, degree of acetylation and ionic strength on surface tension of chitosan in dilute solution. Carbohydrate Polymers, 2006. 64(1): p. 29-36.
189. Huang, M., E. Khor, and L.-Y. Lim, Uptake and Cytotoxicity of Chitosan Molecules and Nanoparticles: Effects of Molecular Weight and Degree of Deacetylation. Pharmaceutical Research, 2004. 21(2): p. 344-353.
190. Prasitsilp M, J.R., Kongsuwan K, Damrongchai N, Watts P, Cellular responses to chitosan in vitro: The importance of deacetylation. Journal of Materials Science: Materials in Medicine, 2000. 11(12): p. 773-778.
191. Chellat, F., et al., Study of biodegradation behavior of chitosan-xanthan microspheres in simulated physiological media. Journal of Biomedical Materials Research, 2000. 53(5): p. 592-599.
192. Zhang, H. and S.H. Neau, In vitro degradation of chitosan by a commercial enzyme preparation: effect of molecular weight and degree of deacetylation. Biomaterials, 2001. 22(12): p. 1653-1658.
193. Cho, Y.-W., et al., Water-soluble chitin as a wound healing accelerator. Biomaterials, 1999. 20(22): p. 2139-2145.
194. Ueno, H., et al., Accelerating effects of chitosan for healing at early phase of experimental open wound in dogs. Biomaterials, 1999. 20(15): p. 1407-1414.
195. Ueno, H., T. Mori, and T. Fujinaga, Topical formulations and wound healing applications of chitosan. Advanced Drug Delivery Reviews, 2001. 52(2): p. 105-115.
196. Francis Suh, J.K. and H.W.T. Matthew, Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials, 2000. 21(24): p. 2589-2598.
197. Haipeng, G., et al., Studies on nerve cell affinity of chitosan-derived materials. J Biomed Mater Res, 2000. 52(2): p. 285-95.
198. Klokkevold, P.R., et al., Osteogenesis Enhanced by Chitosan (Poly-N-Acetyl Glucosaminoglycan) In Vitro. Journal of Periodontology, 1996. 67(11): p. 1170-1175.
199. Lee YM, P.Y., Lee SJ, Ku Y, Han SB, Choi SM, Klokkevold PR, Chung CP., Tissue engineered bone formation using chitosan/tricalcium phosphate sponges. Journal of Periodontology, 2000. 71(3): p. 410-417.
200. Lee, J.E., et al., Effects of a Chitosan Scaffold Containing TGF-β1 Encapsulated Chitosan Microspheres on In Vitro Chondrocyte Culture. Artificial Organs, 2004. 28(9): p. 829-839.
201. Bumgardner, J.D., et al., Contact angle, protein adsorption and osteoblast precursor cell attachment to chitosan coatings bonded to titanium. Journal of Biomaterials Science, Polymer Edition, 2003. 14(12): p. 1401-1409.
202. Lahiji A, S.A., Hungerford DS, Frondoza CG., Chitosan supports the expression of extracellular matrix proteins in human osteoblasts and chondrocytes. Journal of Biomedical Materials Research Part A, 2000. 51(4): p. 586-595.
203. Nettles DL, E.S., Gilbert JA., Potential use of chitosan as a cell scaffold material for cartilage tissue engineering. Tissue Engineering, 2002. 8(6): p. 1009-1016.
204. Bumgardner JD, W.R., Gerard PD, Bergin P, Chestnutt B, Marin M, Ramsey V, Elder SH, Gilbert JA., Chitosan: potential use as a bioactive coating for orthopaedic and craniofacial/dental implants. Journal of Biomaterials Science Polymer, 2003. 14(5): p. 423-438.
205. Zhang, W., et al., Upregulation of BMSCs Osteogenesis by Positively-Charged Tertiary Amines on Polymeric Implants via Charge/iNOS Signaling Pathway. Sci. Rep., 2015. 5.
206. Lee, J.E., et al., Effects of the controlled-released TGF-β1 from chitosan microspheres on chondrocytes cultured in a collagen/chitosan/glycosaminoglycan scaffold. Biomaterials, 2004. 25(18): p. 4163-4173.
207. Garcia-Fuentes, M., D. Torres, and M.J. Alonso, Design of lipid nanoparticles for the oral delivery of hydrophilic macromolecules. Colloids and Surfaces B-Biointerfaces, 2003. 27(2-3): p. 159-168.
208. Garcia-Fuentes, M., D. Torres, and M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin. International Journal of Pharmaceutics, 2005. 296(1-2): p. 122-132.
209. Garcia-Fuentes, M., et al., A comparative study of the potential of solid triglyceride nanostructures coated with chitosan or poly(ethylene glycol) as carriers for oral calcitonin delivery. European Journal of Pharmaceutical Sciences, 2005. 25(1): p. 133-143.
210. Chen, F., et al., In vitro and in vivo study of N-trimethyl chitosan nanoparticles for oral protein delivery. International Journal of Pharmaceutics, 2008. 349(1–2): p. 226-233.
211. Vakilian, S., et al., Structural stability and sustained release of protein from a multilayer nanofiber/nanoparticle composite. International Journal of Biological Macromolecules, 2015. 75: p. 248-257.
212. Hervella, P., et al., PEGylated Lipid Nanocapsules with Improved Drug Encapsulation and Controlled Release Properties. Current Topics in Medicinal Chemistry, 2014. 14(9): p. 1115-1123.
213. de la Fuente, M., et al., Nanoparticles as protein and gene carriers to mucosal surfaces. Nanomedicine, 2008. 3(6): p. 845-857.
214. Smith, D.J. and S. Serhatkulu, Chitosan-based nitric oxide donor compositions, in Google Patents. 2001.
215. Lai, G.-J., et al., Composite chitosan/silk fibroin nanofibers for modulation of osteogenic differentiation and proliferation of human mesenchymal stem cells. Carbohydrate Polymers, 2014. 111(0): p. 288-297.
216. Shalumon, K.T., et al., Modulation of Bone-Specific Tissue Regeneration by Incorporating Bone Morphogenetic Protein and Controlling the Shell Thickness of Silk Fibroin/Chitosan/Nanohydroxyapatite Core–Shell Nanofibrous Membranes. ACS Applied Materials & Interfaces, 2015. 7(38): p. 21170-21181.
217. Roozbahani, F., et al., Effects of Chitosan Concentration on the Protein Release Behaviour of Electrospun Poly(-caprolactone)/Chitosan Nanofibers. Journal of Nanomaterials, 2015. 2015: p. 11.
218. Nista, S.V.G., J. Bettini, and L.H.I. Mei, Coaxial nanofibers of chitosan–alginate–PEO polycomplex obtained by electrospinning. Carbohydrate Polymers, 2015. 127: p. 222-228.
219. Chen, J.-W., et al., Preparation of biocompatible membranes by electrospinning. Desalination, 2008. 233(1-3): p. 48-54.
220. Thien, D.V., Preparation and application of chitosan electrosprayed nanoparticles and electrospun nanofibers, in Department of Chemical Engineering. 2012, National Taiwan University of Science and Technology: Taipei, Taiwan. p. 136.
221. X. Xu, Z., J. F., Cross-linked electrospun fibrous scaffold for tissue engineering. Current Tissue Engineering, 2012. 1(2-14).
222. Tillet, G., B. Boutevin, and B. Ameduri, Chemical reactions of polymer crosslinking and post-crosslinking at room and medium temperature. Progress in Polymer Science, 2011. 36(2): p. 191-217.
223. Yang, S.-l., et al., Thermal and mechanical properties of chemical crosslinked polylactide (PLA). Polymer Testing, 2008. 27(8): p. 957-963.
224. Schiffman, J.D.S., C. L., Cross-linking chitosan nanofibers. Biomacromolecules, 2007. 8: p. 594– 601.
225. Mukherjee, D.P., et al., An animal evaluation of a paste of chitosan glutamate and hydroxyapatite as a synthetic bone graft material. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2003. 67B(1): p. 603-609.
226. Gough, J.E., C.A. Scotchford, and S. Downes, Cytotoxicity of glutaraldehyde crosslinked collagen/poly(vinyl alcohol) films is by the mechanism of apoptosis. J Biomed Mater Res, 2002. 61(1): p. 121-30.
227. Rnjak-Kovacina, J., et al., Tailoring the porosity and pore size of electrospun synthetic human elastin scaffolds for dermal tissue engineering. Biomaterials, 2011. 32(28): p. 6729-6736.
228. Nivison-Smith, L., J. Rnjak, and A.S. Weiss, Synthetic human elastin microfibers: Stable cross-linked tropoelastin and cell interactive constructs for tissue engineering applications. Acta Biomaterialia, 2010. 6(2): p. 354-359.
229. Sisson, K.Z., C. Farach-Carson, M. C. Chase, D. B. Rabolt, J. F., Evaluation of cross-linking methods for electrospun gelatin on cell growth and viability. Biomacromolecules, 2009. 10(7): p. 1675-1680.
230. Sung, H.W., et al., In vitro evaluation of cytotoxicity of a naturally occurring cross-linking reagent for biological tissue fixation. Journal of Biomaterials Science, Polymer Edition, 1999. 10(1): p. 63-78.
231. Butler, M.F., Y.-F. Ng, and P.D.A. Pudney, Mechanism and kinetics of the crosslinking reaction between biopolymers containing primary amine groups and genipin. Journal of Polymer Science Part A: Polymer Chemistry, 2003. 41(24): p. 3941-3953.
232. Bavariya, A.J., et al., Evaluation of biocompatibility and degradation of chitosan nanofiber membrane crosslinked with genipin. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2014. 102(5): p. 1084-1092.
233. Chiono, V., et al., Genipin-crosslinked chitosan/gelatin blends for biomedical applications. Journal of Materials Science: Materials in Medicine, 2008. 19(2): p. 889-898.
234. Bi, L., et al., Effects of different cross-linking conditions on the properties of genipin-cross-linked chitosan/collagen scaffolds for cartilage tissue engineering. Journal of Materials Science: Materials in Medicine, 2011. 22(1): p. 51-62.
235. Mirzae, E. and Faridi-Majidi., Preparation of chitosan based nanofibers as a potential wound dressing by electrospinning. In the 4th International Conference on Nanostructures (ICNS4), Kish Island, I.R Iran, 2012.
236. M.Ignatova, S., K. Markova, N., Manolova, N., Rashkov, I., Electrospun nanofiber mats with antibacterial properties from quaternized chitosan and poly(vinyl alcohol). Carbohydrate Researcg, 2006. 341: p. 2098-2107.
237. Ignatova, M., N. Manolova, and I. Rashkov, Novel antibacterial fibers of quaternized chitosan and poly(vinyl pyrrolidone) prepared by electrospinning. European Polymer Journal, 2007. 43(4): p. 1112-1122.
238. Kurniawan, C., Crosslinking of chitosan electrospun nanofibers by UV-irradiation for tissue engineering scaffolds, in Department of Chemical Engineering. 2013, National Taiwan University of Science and Technology: Taipei, Taiwan. p. 121.
239. Nguyen, C.V., One-step electrospinning of photo-crosslinked chitosan/biphasic calcium phosphate nanofibers, in Department of Chemical Engineering. 2014, National Taiwan University of Science and Technology: Taipei, Taiwan. p. 123.
240. Sionkowska, A., et al., The influence of UV irradiation on the mechanical properties of chitosan/poly(vinyl pyrrolidone) blends. Polymer Degradation and Stability, 2005. 88(2): p. 261-267.
241. Liu, T., et al., Photochemical crosslinked electrospun collagen nanofibers: Synthesis, characterization and neural stem cell interactions. Journal of Biomedical Materials Research Part A, 2010. 95A(1): p. 276-282.
242. Lin, W.-H. and W.-B. Tsai, In situ UV-crosslinking gelatin electrospun fibers for tissue engineering applications. Biofabrication, 2013. 5(3).
243. Langer, R. and J. Vacanti, Tissue engineering. Science, 1993. 260(5110): p. 920-926.
244. Kim, C.H., et al., An improved hydrophilicity via electrospinning for enhanced cell attachment and proliferation. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2006. 78B(2): p. 283-290.
245. Tang, S. and L. Edman, On-demand photochemical stabilization of doping in light-emitting electrochemical cells. Electrochimica Acta, 2011. 56(28): p. 10473-10478.
246. Aduba, D.J., Bachelor of science. Master of Science, Biomedical Engineering, 2008.
247. Siffert, R.S., The role of alkaline phosphatase in osteogenesis. The Journal of Experimental Medicine, 1951. 93(5): p. 415-426.
248. Golub, E.E. and K. Boesze-Battaglia, The role of alkaline phosphatase in mineralization. Current Opinion in Orthopaedics, 2007. 18(5): p. 444-448.
249. Orimo, H., The Mechanism of Mineralization and the Role of Alkaline Phosphatase in Health and Disease. Journal of Nippon Medical School, 2010. 77(1): p. 4-12.
250. Tabatabai, M.A. and J.M. Bremner, Use of p-nitrophenyl phosphate for assay of soil phosphatase activity. Soil Biology and Biochemistry, 1969. 1(4): p. 301-307.
251. Sabokbar, A., et al., A rapid, quantitative assay for measuring alkaline phosphatase activity in osteoblastic cells in vitro. Bone and Mineral, 1994. 27(1): p. 57-67.
252. Smith, P.K., et al., Measurement of protein using bicinchoninic acid. Analytical Biochemistry, 1985. 150(1): p. 76-85.
253. Cho, J., et al., Viscoelastic properties of chitosan solutions: Effect of concentration and ionic strength. Journal of Food Engineering, 2006. 74(4): p. 500-515.
254. Son, W.K., et al., Electrospinning of ultrafine cellulose acetate fibers: Studies of a new solvent system and deacetylation of ultrafine cellulose acetate fibers. Journal of Polymer Science Part B-Polymer Physics, 2004. 42(1): p. 5-11.
255. Koombhongse, S., W.X. Liu, and D.H. Reneker, Flat polymer ribbons and other shapes by electrospinning. Journal of Polymer Science Part B-Polymer Physics, 2001. 39(21): p. 2598-2606.
256. Sangsanoh, P. and P. Supaphol, Stability Improvement of Electrospun Chitosan Nanofibrous Membranes in Neutral or Weak Basic Aqueous Solutions. Biomacromolecules, 2006. 7(10): p. 2710-2714.
257. He, Q., et al., Preparation of chitosan films using different neutralizing solutions to improve endothelial cell compatibility. Journal of Materials Science: Materials in Medicine, 2011. 22(12): p. 2791-2802.
258. Holzbecher, M., O. Knop, and M. Falk, Infrared Studies of Water in Crystalline Hydrates: Sodium Nitroprusside Dihydrate, Na2[Fe(CN)5NO]•2H2O. Canadian Journal of Chemistry, 1971. 49(9): p. 1413-1424.
259. Meng, L., et al., Electrospinning of in situ crosslinked collagen nanofibers. Journal of Materials Chemistry, 2012. 22(37): p. 19412-19417.
260. Keogh, M.B., F.J. O’Brien, and J.S. Daly, Substrate stiffness and contractile behaviour modulate the functional maturation of osteoblasts on a collagen–GAG scaffold. Acta Biomaterialia, 2010. 6(11): p. 4305-4313.
261. Chatterjee, K., et al., The effect of 3D hydrogel scaffold modulus on osteoblast differentiation and mineralization revealed by combinatorial screening. Biomaterials, 2010. 31(19): p. 5051-5062.
262. Rodrigues, C.A., et al., The preparation and characterization of the hexacyanides immobilized in chitosan. Journal of the Brazilian Chemical Society, 1997. 8(1): p. 07-11.
263. Ralston, S.H., et al., Human osteoblast-like cells produce nitric oxide and express inducible nitric oxide synthase. Endocrinology, 1994. 135(1): p. 330-336.
264. Bakolitsa, C., et al., Structural basis for vinculin activation at sites of cell adhesion. Nature, 2004. 430(6999): p. 583-586.
265. Keselowsky, B.G., D.M. Collard, and A.J. García, Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation. Proceedings of the National Academy of Sciences, 2005. 102(17): p. 5953-5957.
266. Haÿ, E., et al., N- and E-cadherin mediate early human calvaria osteoblast differentiation promoted by bone morphogenetic protein-2. Journal of Cellular Physiology, 2000. 183(1): p. 117-128.
267. Liu, S.M. and T. Sundqvist, Nitric Oxide and cGMP Regulate Endothelial Permeability and F-Actin Distribution in Hydrogen Peroxide-Treated Endothelial Cells. Experimental Cell Research, 1997. 235(1): p. 238-244.
268. Jun, C.-D., et al., Nitric Oxide Induces ADP-Ribosylation of Actin in Murine Macrophages: Association with the Inhibition of Pseudopodia Formation, Phagocytic Activity, and Adherence on a Laminin Substratum. Cellular Immunology, 1996. 174(1): p. 25-34.
269. Lai, C.-F., et al., Erk Is Essential for Growth, Differentiation, Integrin Expression, and Cell Function in Human Osteoblastic Cells. Journal of Biological Chemistry, 2001. 276(17): p. 14443-14450.
270. Rangaswami, H., et al., Type II cGMP-dependent Protein Kinase Mediates Osteoblast Mechanotransduction. Journal of Biological Chemistry, 2009. 284(22): p. 14796-14808.
271. Aubin, J.E., Osteoprogenitor cell frequency in rat bone marrow stromal populations: Role for heterotypic cell–cell interactions in osteoblast differentiation. Journal of Cellular Biochemistry, 1999. 72(3): p. 396-410.
272. Kii, I., et al., Cell-Cell Interaction Mediated by Cadherin-11 Directly Regulates the Differentiation of Mesenchymal Cells Into the Cells of the Osteo-Lineage and the Chondro-Lineage. Journal of Bone and Mineral Research, 2004. 19(11): p. 1840-1849.
273. Civitelli, R., Cell–cell communication in the osteoblast/osteocyte lineage. Archives of Biochemistry and Biophysics, 2008. 473(2): p. 188-192.
274. Stains, J.P. and R. Civitelli, Cell-to-cell interactions in bone. Biochemical and Biophysical Research Communications, 2005. 328(3): p. 721-727.
275. Stains, J.P. and R. Civitelli, Cell-cell interactions in regulating osteogenesis and osteoblast function. Birth Defects Research Part C: Embryo Today: Reviews, 2005. 75(1): p. 72-80.
276. Salasznyk, R.M., et al., Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells. Experimental Cell Research, 2007. 313(1): p. 22-37.
277. Bhattarai, N., et al., Electrospun chitosan-based nanofibers and their cellular compatibility. Biomaterials, 2005. 26(31): p. 6176-6184.
278. Fraser, M., et al., Regulation of p53 and suppression of apoptosis by the soluble guanylyl cyclase//cGMP pathway in human ovarian cancer cells. Oncogene, 2005. 25(15): p. 2203-2212.
279. Mostafa, N.Z., et al., In Vitro Osteogenic Induction Of Human Gingival Fibroblasts For Bone Regeneration. The Open Dentistry Journal, 2011. 5: p. 139-145.
280. Stephens, P., et al., Skin and oral fibroblasts exhibit phenotypic differences in extracellular matrix reorganization and matrix metalloproteinase activity. British Journal of Dermatology, 2001. 144(2): p. 229-237.
281. Sukotjo, C., et al., Oral Fibroblast Expression of wound-inducible transcript 3.0 (wit3.0) Accelerates the Collagen Gel Contraction in Vitro. Journal of Biological Chemistry, 2003. 278(51): p. 51527-51534.
282. Zhou, Y., et al., Osteogenic and Adipogenic Induction Potential of Human Periodontal Cells. Journal of Periodontology, 2008. 79(3): p. 525-534.
283. Baek, M.W., et al., Nitric oxide induces apoptosis in human gingival fibroblast through mitochondria-dependent pathway and JNK activation. International Endodontic Journal, 2015. 48(3): p. 287-297.
284. Noda, M., et al., cDNA cloning of alkaline phosphatase from rat osteosarcoma (ROS 17/2.8) cells. Journal of Bone and Mineral Research, 1987. 2(2): p. 161-164.
285. Stein, S.G., et al., The Onset and Progression of Osteoblast Differentiation is Functionally Related to Cellular Proliferation. Connective Tissue Research, 1989. 20(1-4): p. 3-13.
286. Stein, G.S., J.B. Lian, and T.A. Owen, Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. The FASEB Journal, 1990. 4(13): p. 3111-23.
287. Koyama, A., et al., Nitric oxide accelerates the ascorbic acid-induced osteoblastic differentiation of mouse stromal ST2 cells by stimulating the production of prostaglandin E2. European Journal of Pharmacology, 2000. 391(3): p. 225-231.
288. Mancini, L., et al., The Biphasic Effects of Nitric Oxide in Primary Rat Osteoblasts Are cGMP Dependent. Biochemical and Biophysical Research Communications, 2000. 274(2): p. 477-481.
289. Yamamoto, K., et al., Direct conversion of human fibroblasts into functional osteoblasts by defined factors. Proceedings of the National Academy of Sciences, 2015. 112(19): p. 6152-6157.
290. Lee, S.-K., et al., Nitric Oxide Modulates Osteoblastic Differentiation with Heme Oxygenase-1 <i>via</i> the Mitogen Activated Protein Kinase and Nuclear Factor-kappaB Pathways in Human Periodontal Ligament Cells. Biological and Pharmaceutical Bulletin, 2009. 32(8): p. 1328-1334.
291. Carnes, D.L., C.L. Maeder, and D.T. Graves, Cells With Osteoblastic Phenotypes Can Be Explanted From Human Gingiva and Periodontal Ligament. Journal of Periodontology, 1997. 68(7): p. 701-707.
292. Butler, W.T., The Nature and Significance of Osteopontin. Connective Tissue Research, 1989. 23(2-3): p. 123-136.
293. Datta, N., et al., In vitro generated extracellular matrix and fluid shear stress synergistically enhance 3D osteoblastic differentiation. Proceedings of the National Academy of Sciences of the United States of America, 2006. 103(8): p. 2488-2493.
294. Chang, P.C., et al., Bone tissue engineering with novel rhBMP2-PLLA composite scaffolds. J Biomed Mater Res A, 2007. 81(4): p. 771-80.
295. Damoulis, P.D., et al., Osteogenic differentiation of human mesenchymal bone marrow cells in silk scaffolds is regulated by nitric oxide, in Annals of the New York Academy of Sciences. 2007. p. 367-376.
296. Hoang, Q.Q., et al., Bone recognition mechanism of porcine osteocalcin from crystal structure. Nature, 2003. 425(6961): p. 977-980.